Use of nitrogen-containing complexing agents for deodorization and antimicrobial treatment of the skin and textile fibre materials

ABSTRACT

The present invention relates to the use of nitrogen-containing complexing agents for deodorization and antimicrobial treatment of the skin and of textile fiber materials. 
     The complexing agents employed according to the invention have the formula                    
     in which 
     Q 1 , is Carb 1 ; Carb 2, ; or a radical of the formula —(CH 2 ) m     1   —OH; 
     Q 2  is hydrogen or Carb 2 ; and 
     Q 3  is Carb 3 ; an amino acid radical; or a radical of the formula                    
     where Carb 1 , Carb 2  and Carb 3  independently of one another are the radical of a C 1 -C 8 -mono- or -dicarboxylic acid and m 1  is 1 to 5. 
     The complexing agents according to the invention show a pronounced bacteriostatic action against  Corynebacterium xerosis  (bacteria which cause body odour) and are therefore suitable as the antimicrobial active substance in body care compositions and antimicrobial fabric finishing of textile materials.

The present invention relates to the use of nitrogen-containingcomplexing agents for deodorization and antimicrobial treatment of theskin and of textile fibre materials.

It is known that various nitrogen-containing complexing agents, forexample ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid(NTA), β-alaninediacetic acid (EDETA) or ethylenediaminedisuccinic acid(EDDS) are widely employed in domestic detergents because of theircomplexing properties.

Surprisingly, it has been found that certain nitrogen-containingcomplexing agents also have an antimicrobial action againstGram-positive bacteria and are therefore particularly suitable fordeodorization and antimicrobial treatment of the human skin and oftextile fibre materials.

The present invention therefore relates to the use ofnitrogen-containing complexing agents for antimicrobial treatment of theskin and of textile fibre materials.

Compounds which are preferably used according to the invention ascomplexing agents are those of the formula

in which

Q₁, is Carb₁; Carb₂,; or a radical of the formula —(CH₂)_(m) ₁ —OH;

Q₂ is hydrogen or Carb₂; and

Q₃ is Carb₃; an amino acid radical; or a radical of the formula

where Carb₁, Carb₂ and Carb₃ independently of one another are theradical of a C₁-C₈-mono- or dicarboxylic acid; and

m₁ is 1 to 5.

Compounds which are particularly preferred here are those of the formula(1) in which the amino acid radical Q₃ has the formula

and especially compounds of the formula (1) in which

Q₁ is a monocarboxylic acid; or a radical of the formula —(CH₂)_(m) ₁—OH;

Q₂ is hydrogen or a monocarboxylic acid; and

Q₃ is formula (1b); or a monocarboxylic acid.

Complexing agents which are of particular interest are those of theformula (1) in which Carb₂ and Carb₃, independently of one another arethe radical of the formula

—[(CH₂)]_(n) ₁ —COOH,  (1c )

in which

n₁ is 0 to 5.

Complexing agents which are important in practice have the formula

or the formula

Nitrilotriacetic acid (NTA) is furthermore suitable as the complexingagent.

Other examples of complexing agents which can be employed according tothe invention are aminotrimethylenephosphoric acid (ATMP) of the formula

serinediacetic acid (SDA) of the formula

asparaginediacetic acid of the formula

methylglycinediacetic acid (MGDA) of the formula (7)

The nitrogen-containing complexing agents employed according to theinvention can be employed not only as the acid but also in the form ofthe water-soluble salts, preferably as lithium, sodium, potassium,ammonium and ethanolammonium salts.

Ethylenediaminedisuccinic acid (EDDS) of the formula (2) has twoasymmetric carbon atoms. Various stereoisomeric forms of this compoundare therefore possible. The (S,S) configuration of EDDS has the formula

An inexpensive chemical synthesis leads to a mixture of the three formsS,S; R,R; and meso-EDDS. However, separation of these stereoisomericcompounds requires a high industrial expenditure. Optically pure(S,S)-EDDS can be prepared with the aid of an Actinomycetes strain (T.Nishikiori et al., Production by Actinomycetes of(S,S)-N,N′-ethylenediaminedisuccinic acid, an inhibitor of phospholipasec; J.Antibiotics 37, 426-427 (1984)).

The purely chemical preparation of the compound of the formula (9) iscarried out in a manner known per se, such as is described, for example,by J. A. Neal, N. Rose in Inorganic Chemistry,7, 2405 (1985).

Racemic EDDS can be prepared in accordance with U.S. Pat. No. 3,158,635.

The complexing agents according to the invention show a pronouncedbacteriostatic action, in particular against Gram-positive bacteria ofthe skin flora, for example Corynebacterium xerosis (bacteria whichcauses body odour). They are therefore particularly suitable as theantimicrobial active substance in body care compositions, for examplesoaps, shampoos, foot care products and, in particular, deodorants, aswell as an additive in detergents.

The invention therefore also relates to a body care compositioncomprising at least one nitrogen-containing complexing agent andcarriers or auxiliaries which are tolerated in comsetics.

The body care composition according to the invention comprises 0.01 to15, preferably 0.5 to 10, % by weight, based on the total weight of thecomposition, of a nitrogen-containing complexing agent and auxiliarieswhich are tolerated in cosmetics.

Depending on the form in which the body care composition is present, italso comprises, in addition to the complexing agent, other constituents,for example sequestering agents, dyes, perfume oils, thickeners orconsolidating agents (consistency regulators), emmollients, UVabsorbers, skin protection agents, antioxidants, additives which improvethe mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca,or Mg salts of C₁₄-C₂₂ fatty acids, and, if appropriate, preservatives.

Because of their good water-solubility, the complexing agents accordingto the invention can be incorporated into the corresponding formulationswithout problems.

The body care compositions according to the invention can be formulatedas a water-in-oil or oil-in-water emulsion, as alcoholic or alcoholcontaining formulation, as a vesicular dispersion of an ionic ornonionic amphiphilic lipid, as a gel or solid stick or as an aerosolformulation.

As a water-in-oil or oil-in-water emulsion, the auxiliary which istolerated in cosmetics preferably comprises 5 to 50% of an oily phase, 5to 20% of an emulsifier and 30 to 90% of water. The oily phase cancomprise any oil suitable for cosmetic formulations, for example one ormore hydrocarbon oils, a wax, a naturally occurring oil, a silicone oil,a fatty acid ester or a fatty alcohol. Preferred mono- or polyols areethanol, isopropanol, propylene glycol, hexylene glycol, glycerol andsorbitol.

An anitmicrobial soap has, for example, the following composition:

0.01 to 5% by weight of the compound of the formula (2)

0.3 to 1% by weight of titanium dioxide

1 to 10% by weight of stearic acid

to 100% of soap base, for example the sodium slats of tallow fatty andcoconut fatty acid or glycerols.

A shampoo has, for example, the following composition:

0.01 to 5% by weight of the compound of the formula (2),

12.0% by weight of sodium laureth-2-sulfate,

4.0% by weight of cocamidopropylbetaine,

3.0% by weight of NaCl and

water to 100%.

A deodorant has, for example, the following composition:

0.01 to 5% by weight of the compound of the formula (2),

60% by weight of ethanol,

0.3% by weight of perfume oil and

water to 100%.

The complexing agents according to the invention are furthermoresuitable for the treatment of textile fibre materials. The fibrematerials are non-dyed and dyed or printed fibre materials, for exampleof silk, leather, wool, polyamide or polyurethanes, and in particularall types of cellulosic fibre materials. Such fibre materials are, forexample, naturally occurring cellulosic fibres, such as cotton, linen,jute and hemp, and cellulose and regenerated cellulose. Textile fibrematerials which are preferably suitable are those of cotton.

The following examples serve to illustrate the invention.

EXAMPLE 1 Determination of the Antimicrobial Activities of S,S-EDDS,R,R-EDDS, Racemate of EDDS and EDETA, EDTA and NTA

Test method: An agar diffusion test is carried out with the followingmodifications:

Medium: casein-soya flour peptone agar (caso-agar)

Test organisms: Corynebacterium xerosis ATCC 373 Corynebacterium xerosisATCC 7711 Corynebacterium minutissimum ATCC 23358

Procedure: 500 ml of caso-agar are innoculated with 3.5 ml of anovernight culture of the bacteria, diluted 1:100, and caso plates (18ml) are covered with a layer of about 5 ml of the bacteria-containingagar. After the plates have cooled, holes of diameter 1 cm are stampedout with a cork borer. Each stamped-out hole is filled with in each case100 μl of a test substance dilution and the plates are incubated at 37°C. for 2 days. Double-distilled water is employed as the solvent for allthe substances. In the case of EDETA GS, the pH is adjusted to 3.3 byaddition of 1 N NaOH. Chemically prepared S,S-EDDS is adjusted to the pHof 5.6 by addition of 1 N NaOH.

Controls: Double-distilled water

The test results are listed in Table 1:

TABLE 1 Concen- Inhibitory aureola diameter tration Cory. xerosis Cory.xerosis Substance [ppm] ATTC 7711 ATTC 373 EDETA 10000 5/5¹ 1/1¹S,S-EDDS 10000 15/15¹ 10/10¹ (prepared chemically) S,S-EDDS 10000 15/15¹10/10¹ (prepared by fermentation) EDTA 10000 2/2 5/5 R,S-EDDS 10000 n.d.12/13 R,R-EDDS 10000 n.d. 15/15 ¹Slight growth on inhibitory aureolas

The test results show that both EDETA, EDTA and the EDDS prepared byfermentation and chemically (=R,R; S,S; R,S) show a pronouncedbacteriostatic action against Corynebacterium xerosis.

Examples of Formulations Having a Bacteriostatic Action

EXAMPLE 2 Preparation of a Washing Powder

Laurylammonium sulfate 8.0% Nonionic surfactants 2.9% Soaps 3.5% Sodiumtripolyphosphate 43.8% Sodium silicate 7.5% Magnesium silicate 1.9%Carboxymethylcellulose 1.2% EDTA 0.2% Sodium sulfate 21.2% EDDS 1% Waterto 100%

The formulation is prepared as follows:

The solid components are mixed and homogenized in a mortar and stirredwith deionized water until a uniform pourable and pumpable paste(slurry) is obtained, which is finally spray-dried.

EXAMPLE 3 Preparation of a Cleansing Tonic

Ethanol 20% Glycerol 5% PEG-40 hydrogenated castor oil 1% (hydrogenatedethoxylated castor oil) EDDS 0.5% Perfume ad libidum Water to 100%

The formulation is prepared as follows:

EDDS is dissolved in ethanol. Under stirring at room temperature PEG-40,glycerol and perfume are added. Finally, the water is added.

EXAMPLE 3 Preparation of a Deodorant Stick

Ethanol 20% Glycerol 30% Propylene glycol 20% Ceteareth-25 3% (=ethoxylated cetyl/stearyl alcohol) Sodium stearate 7% EDDS 0, 5% Perfumead libidum Water to 100%

The formulation is prepared as follows:

Sodium stearate is melted at 60° C. Propylene glycol, Cetearath-25 andglycerol are added to the melting until a homogeneous clear suspensionis obtained. Finally, the suspension is stirred with a EDDS-solution inan alcohol/water mixture at 50° C. and cooled slowly.

EXAMPLE 4 Preparation of Soluble EDDS Salts and Deodorant Formulations

S,S-EDDS is obtained by means of microbiological (WO 96/36725) orchemical synthesis (J. A. Neal et al., Inorg.Chem. 7, 2405 (1968)).Racemic EDDS is prepared from maleic anhydride and ethylenediamine (U.S.Pat. No. 3,158,635).

A 1% suspension of racemic EDDS or S,S-EDDS is prepared in water/ethanol(about 7:3) with vigorous stirring. An aqueous solution of NaOH ismetered in with an autoamtic titration device until the pH of 7 remainsconstant for 30 minutes. Any slight milky clouding which occurs isremoved by filtering through paper.

By addition of a thickener like hydroxy ethyl cellulose a cleardeodorant formulation which is stable at room temperature, comprisesabout 1% of active substance (based on the tetra-acid) and has askin-friendly pH is obtained.

If NaOH is replaced by KOH, ammonia or ethanolamine, the correspondingpotassium, ammonium and ethanolammonium salts are obtained. Lithiumhydroxide, sodium carbonate, sodium bicarbonate or laurylamine can alsobe employed as the base.

EXAMPLE 5 Detection of the Substantial Antimicrobial Activity ofR,S-EDDS Salts on the Skin

Formulations 1% of R,S-EDDS/sodium salt (Solutions in 30% ethanol): 1%of R,S-EDDS/amine salt (for the preparation, cf. Example 4) Medium:Casein-soya flour peptone agar (caso-agar) Test organism:Corynebacterium xerosis ATCC 373

Test method:

Before application of the test solutions, the underarms are washed witha non-antimicrobial soap twice for 1 minute each time. A total of 6 mlof test product is then applied to the washed, dry skin of the underarm.Immediately and 2 hours after application of the test products, the EDDSon the skin is extracted by means of discs of filter paper (2 cmdiameter) moistened in 0.9% NaCl solution (pH: 8.2). For this, the moistfilter disc is placed on the treated skin without airbubbles for 4minutes. The filter discs are subsequently dried at room temperature andthen placed on solid agar media with test bacteria.

To prepare the solid agar media, 500 ml of liquid agar are innoculatedwith 3.5 ml of a 12-16-hour culture, diluted 1:100, of the test bacteriaat 47° C. and caso plates (18 ml) are covered with a layer of about 5 mlof the bacteria-containing agar.

After the filter discs have been placed on top, the agar media areincubated for 2 days at 37° C. and the inhibition under the filter discor the inhibitory aureolas of the filter discs is/are then determined.

The test results are listed in Table 2:

TABLE 2 Substance Inhibitory aureola dia- meter (mm)/inhibition underthe filter disc* Coryneb. xerosis ATCC 373 Placebo 0/0 R,S-EDDS (sodiumsalt) imme- 5/4 diately 2 hours 3/4 after application R,S-EDDS (Aminesalt) imme- 2, 5/4 diately 2 hours 2/4 after application *Inhibitionunder the filter disc: Explanation: 0 = good growth (no inhibition) 2 =inhibited but clear growth (weak inhibition) 4 = no growth (potentinhibition)

The test results show that a pronounced inhibition of Corynebacteriumxerosis is achieved with both test substances.

The test shows that sufficiently high concentrations of EDDS to achieveinhibition of Corynebacterium xerosis are also still present on the skin2 hours after the last application.

What is claimed is:
 1. A method of antimicrobial treatment of the skinor of textile fibre materials which comprises contacting them with anantimicrobially effective amount of a nitrogen-containing complexingagent of the formula


2. A method according to claim 1 wherein the nitrogen-containingcomplexing agent of the formula (2) is in the form of its (S,S), (R,S)or (R,R) stereoisomer.
 3. A method according to claim 1, wherein thecomplexing agent is in the form of one of its water-soluble salts.
 4. Amethod according to claim 3, wherein the complexing agent is present inthe form of its lithium, sodium, potassium, ammonium or ethanolammoniumsalt.
 5. A method of combating Gram-positive bacteria which comprisescontacting them with an antimicrobially effective amount of anitrogen-containing complexing agent according to claim
 1. 6. A methoddisinfecting textile fibre materials, which comprises contacting saidmaterials with an antimicrobially effective amount of anitrogen-containing complexing agent according to claim 1.